Immunophenotypic characterization of relapsed chronic lymphocytic leukemia patients treated with lumiliximab in combination with FCR

Abstract

7067 Background: Lumiliximab is an anti-CD23 monoclonal antibody under investigation for the treatment of patients with relapsed B-cell chronic lymphocytic leukemia (BCLL). A comprehensive immunophenotypic characterization of CLL cells obtained from patients treated with lumiliximab in combination with fludarabine, cyclophosphamide, and rituximab (L + FCR) was conducted. This included an analysis of the frequency of BCLL cells (CD5+CD19+), expression levels of CD38 (a negative prognostic factor), CD55 and CD59 (potential resistance markers of rituximab therapy). Methods: Immunophenotypic characterization was performed by four color flow cytometry analysis. BCLL cells were first identified by gating on viable CD45+ cells and subselecting with antibodies to CD5 and CD19 receptors. Antigen expression levels and their frequencies were reported in terms of mean fluorescence intensities (MFI) and fraction (%) of positive BCLL cells. Results: The analysis of peripheral blood samples from L + FCR treated patients indicated a substantial decrease in CD5+CD19+ cells in 30 of the 31 evaluable patients, although, the time to CLL count reduction following therapy was variable, ranging from week 1 to week 13. Clinical activity was observed in patients with both high (>30%) and low (<30%) levels of CD38 expression (MFI 6 - 230). Finally, clinical activity of L +FCR was independent of pre-treatment expression levels of CD55 (MFI 45–272) and CD59 antigen (MFI 20–191) and was also observed in a few patients showing increased expression of CD59 receptor, compared with their individual pre-treatment values, which has been associated with resistance to single agent rituximab. Conclusions: Clinically, L + FCR is an effective regimen in decreasing tumor burden in the peripheral blood of patients with BCLL. Importantly, the clinical activity of L + FCR appears to be independent of CD38 expression (a poor prognostic factor) and thereby may provide clinical benefit to a subset of patients with unfavorable clinical outcomes. Clinical activity was also observed in patients with BCLL expressing high levels of CD59 antigen, thus, suggesting a different MOA than other mAbs active in this indication such as Rituxan. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Biogen Idec Biogen Idec Biogen Idec